Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.
Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid β-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3β was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3β phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3β by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3β-related signaling pathways.
These differentially expressed genes likely represent biomarkers for early detection of colorectal cancer and may be potential therapeutic targets after confirmed by further studies.
This study aimed to investigate the expression and clinical significance of enoyl coenzyme A hydratase, short chain, 1 (ECHS1), in patients with colorectal cancer (CRC). The ECHS1 protein expression as detected by immunohistochemistry in 148 CRC specimens was evaluated and compared by clinical pathology and prognosis; 38 specimens from proximal non-cancerous colorectal tissues were included as controls. The ECHS1 protein expression was also measured by western blot analysis in 46 fresh CRC tissue specimens and 22 normal colorectal tissue specimens. The rate of positive ECHS1 expression differed significantly between the CRC tissues (56.76%, 84/148) and the proximal non-cancerous colorectal tissues (5.26%, 2/38) (P<0.001). The ECHS1 protein expression was confirmed not to be associated with gender or age. However, the positive expression of ECHS1 tended to be positively associated with clinical TNM stage (P=0.015), lymph node metastasis (P=0.011) and histological differentiation (P=0.028). The expression of the ECHS1 protein on western blot analysis was significantly increased in CRC vs. normal tissues. In addition, the overall survival curves estimated with the Kaplan-Meier method demonstrated that CRC patients exhibiting low ECHS1 expression survived significantly longer compared to patients with high ECHS1 levels (P=0.039). Our data suggested that ECHS1 protein expression may contribute to the occurrence, progression and metastasis of CRC, is closely associated with prognosis and may provide useful information for CRC molecular-targeted therapy.
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